This study suggests a new erythrocyte sedimentation rate (ESR) measurement method for the biophysical assessment of blood by using a microfluidic device. For an effective ESR measurement, a disposable syringe filled with blood is turned upside down and aligned at 180 with respect to gravitational direction. When the blood sample is delivered into the microfluidic device from the top position of the syringe, the hematocrit of blood flowing in the microfluidic channel decreases because the red blood cell-depleted region is increased from the top region of the syringe. The variation of hematocrit is evaluated by consecutively capturing images and conducting digital image processing technique for 10 min. The dynamic variation of ESR is quantitatively evaluated using two representative parameters, namely, time constant (k) and ESR-area (A ESR ). To check the performance of the proposed method, blood samples with various ESR values are prepared by adding different concentrations of dextran solution. k and A ESR are quantitatively evaluated by using the proposed method and a conventional method, respectively. The proposed method can be used to measure ESR with superior reliability, compared with the conventional method. The proposed method can also be used to quantify ESR of blood collected from malaria-infected mouse under in vivo condition. To indirectly compare with the results obtained by the proposed method, the viscosity and velocity of the blood are measured using the microfluidic device. As a result, the biophysical properties, including ESR and viscosity of blood, are significantly influenced by the parasitemia level. These experimental demonstrations support the notion that the proposed method is capable of effectively monitoring the biophysical properties of blood. V C 2014 AIP Publishing LLC. [http://dx

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Phosphatase of regenerating liver (PRL)-3, a member of a subgroup of protein tyrosine phosphatases that can stimulate the degradation of the extracellular matrix, is over-expressed in metastatic colorectal cancer (CRC) relative to primary tumors. To determine whether PRL-3-induced enhancement of migration and invasion is dependent on the expression of matrix metalloproteinases (MMPs), PRL-3 was expressed in DLD-1 human CRC cells. The motility, migration and invasion characteristics of the cells were examined, and metastasis to the lung was confirmed in a nude mouse using PRL-3-overexpressing DLD-1 cells [DLD-1 (PRL-3)]. Migration and invasion of the cells were inhibited by phosphatase and farnesyltransferase inhibitors. Expression of MMPs was enhanced 3-to 10-fold in comparison to control cells, and migration and invasion were partially inhibited by small interfering RNA (siRNA) knockdown of MMP-2, -13 or -14. Importantly, siRNA knockdown of MMP-7 completely inhibited the migration and invasion of DLD-1 (PRL-3) cells, whereas overexpression of MMP-7 increased migration. The expression of MMP-7 was also downregulated by phosphatase and farnesyltransferase inhibitors. It was found that PRL-3 induced MMP-7 through oncogenic pathways including PI3K/AKT and ERK and that there is a relationship between the expression of PRL-3 and MMP-7 in human tumor cell lines. The expression of MMP-13 and -14 was very sensitive to the inhibition of farnesyltransferase; however, the migration and invasion of DLD-1 (PRL-3) cells did not strongly depend on the expression of MMP-13 or -14. These results suggest that the migration and invasion of PRL-3-expressing CRC cells depends primarily on the expression of MMP-7.

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The malaria parasite Plasmodium falciparum (Pf) changes the structure and mechanical properties of red blood cells (RBCs). These changes decrease deformability and increase cytoadherence of Pf-infected RBCs to the vascular endothelium, eventually leading to flow occlusions in capillary vessels. In this study, to detect Pf-infected RBCs effectively, deformability and viscosity of blood sample are measured simultaneously and indirectly by quantifying blood flow in a microfluidic device. The microfluidic device is designed by mimicking a Wheatstone-bridge electric circuit. To measure RBC deformability, a deformability assessment chamber (DAC) at the left lower side channel has parallel microfluidic filters. After delivering blood sample and 1× PBS solution at the same flow rate, hemodynamic properties are measured using a time-resolved microparticle image velocimetry technique. Blood volume delivered into the DAC for 200 s is evaluated as a deformability index. Subsequently, blood viscosity is quantified by monitoring blood-filled width of parallel flows in the microfluidic device. The proposed method is applied to evaluate variations in biophysical properties of blood samples partially mixed with normal RBCs and hardened RBCs. As a result, RBC deformability is more effective than blood viscosity in the detection of blood samples with hardened RBC volume fraction of 5%. The microfluidic device is also applied to detect Pf-infected RBCs. When parasitemia is greater than 0.515% for ring stage, 0.0544% for trophozoite stage, and 0.0054% for schizont stage, the measured velocity fields show unstable behavior because of cytoadherence of Pf-infected RBCs. Blood volume delivered into the DAC significantly decreases with increasing parasitemia. The experimental method proposed in this study can detect Pf-infected RBCs with good accuracy.

Red blood cell (RBC) deformability has been considered a potential biomarker for monitoring pathological disorders. High throughput and detection of subpopulations in RBCs are essential in the measurement of RBC deformability. In this paper, we propose a new method to measure RBC deformability by evaluating temporal variations in the average velocity of blood flow and image intensity of successively clogged RBCs in the microfluidic channel array for specific time durations. In addition, to effectively detect differences in subpopulations of RBCs, an air compliance effect is employed by adding an air cavity into a disposable syringe. The syringe was equally filled with a blood sample (V(blood) = 0.3 mL, hematocrit = 50%) and air (V(air) = 0.3 mL). Owing to the air compliance effect, blood flow in the microfluidic device behaved transiently depending on the fluidic resistance in the microfluidic device. Based on the transient behaviors of blood flows, the deformability of RBCs is quantified by evaluating three representative parameters, namely, minimum value of the average velocity of blood flow, clogging index, and delivered blood volume. The proposed method was applied to measure the deformability of blood samples consisting of homogeneous RBCs fixed with four different concentrations of glutaraldehyde solution (0%-0.23%). The proposed method was also employed to evaluate the deformability of blood samples partially mixed with normal RBCs and hardened RBCs. Thereafter, the deformability of RBCs infected by human malaria parasite Plasmodium falciparum was measured. As a result, the three parameters significantly varied, depending on the degree of deformability. In addition, the deformability measurement of blood samples was successfully completed in a short time (∼10 min). Therefore, the proposed method has significant potential in deformability measurement of blood samples containing hematological diseases with high throughput and precise detection of subpopulations in RBCs.

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The global profiling of cardiac ischemia-related genes provides the possible mechanisms of IR and IPC and ways of treating IR injury.